Abstract 2983: A synthetic derivative of 1,2,3-triazole-pyrimidine hybrid reverses multidrug resistance mediated by MRP7

Abstract

Abstract Multidrug resistance protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to transport a wide range of chemotherapeutic agents including taxanes, epothilone B, vinca alkaloids, daunorubicin and etoposide. In our previous study, a 1,2,3-triazole-pyrimidine hybrid 25 was synthesized and found significantly reversing multidrug resistance (MDR) mediated by ABCB1. In this study, we evaluated the efficacy of compound 25 in reversing MDR mediated by MRP7 in vitro. The results showed that 25 significantly sensitized cells overexpressing MRP7 to anticancer drugs that are MRP7 substrates at 3 μ;;M. Mechanism study showed that 25 reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or intracellular localization. Ligand-protein interactions were also modeled by docking with homology MRP7 model. Since limited researches on synthetic MRP7 modulators have been published, our findings provide a valuable prototype for structures which have the potential to be used in combination with conventional anticancer drugs to overcome MDR-mediated by MRP7. Citation Format: Jing-Quan Wang, Zi-Ning Lei, Qiu-Xu Teng, Bo Wang, Li-Ying Ma, Hong-Min Liu, Zhe-Sheng Chen. A synthetic derivative of 1,2,3-triazole-pyrimidine hybrid reverses multidrug resistance mediated by MRP7 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2983.